Triplets versus doublets in the treatment of right-sided metastatic colorectal cancer in real-world setting: A propensity-score weighting analysis.

Abstract

55 Background: Right-sided metastatic colorectal cancer (mCRC) has a worse prognosis and the best first-line treatment is still uncertain. The aim of this study was to analyze progression-free survival (PFS) and overall survival (OS) comparing triplet versus doublet backbone chemotherapy in first-line setting for right-sided mCRC. Methods: Retrospective study evaluating 510 patients with mCRC who were treated in a private institution in Brazil from January 2011 to December 2019. Information of 118 patients with right-sided primary tumor was analyzed in this study. Demographic and clinical data were retrieved from electronic medical records. PFS and OS were calculated in months (m) using propensity-score weighting analysis (PSWA) due to expected disparity between the number of patients treated with triplet and doublet regimens. Variables used to balance patient groups were age; metastasectomy; primary tumor resection; bevacizumab use; BRAF and RAS mutation status. Results: The median follow-up was 31 months. Our population was mostly composed of elderly (64%) and female (52%) patients. First-line treatment with triplet backbone chemotherapy was done in 16 patients (14%). Primary tumor resection was done in 14% of the cases, 55% underwent metastasectomy, and 57% received anti-VEGF treatment. BRAF mutation was found in 9% of the patients and RAS mutation in 46%. After PSWA we found a significant better median PFS among patients treated with triplet regimen: 12.7m versus 8.9m compared to those receiving doublet backbone chemotherapy, with a hazard ratio of 0.64 (CI 95%: 0.42 – 0.97); p-value: 0.037. No significant difference was found in OS (29.8m versus 45.5m) between triplet and doublet therapy groups, respectively. Conclusions: In our study we found a significantly better PFS with triplet backbone chemotherapy in first-line setting for right-sided mCRC, encouraging the use of this regimen in treatment-naive selected patients. However, no difference in OS was found, probably due to subsequent treatments. PSWA is an acceptable and needed tool to enable retrospective real world studies involving treatments with expected uneven distribution. More studies are needed to answer the best strategy to target right-sided mCRC, which remains a challenge for oncologists, with unmet needs.